Intermolecular Insertion of an N,N-Heterocyclic Carbene into a Nonacidic C-H Bond: Kinetics, Mechanism and Catalysis by (K-HMDS)2 (HMDS=Hexamethyldisilazide)

GC Lloyd-Jones, RW Alder, GJJ Owen-Smith

Research output: Contribution to journalArticle (Academic Journal)peer-review

36 Citations (Scopus)

Abstract

The reaction of 2-[13C]-1-ethyl-3-isopropyl-3,4,5,6-tetrahydropyrimidin-1-ium hexafluorophosphate ([13C1]-1-PF6) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide ((K-HMDS)2) in toluene generates 2-[13C]-3-ethyl-1-isopropyl-3,4,5,6-tetrahydropyrimid-2-ylidene ([13C1]-2). The hindered meta-stable N,N-heterocyclic carbene [13C1]-2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2-[13C]-2-benzyl-3-ethyl-1-isopropylhexahydropyrimidine ([13C1]-14) through formal CH insertion of C(2) (the carbene carbon) at the toluene methyl group. Despite a significant pKa mismatch (pKa 1+ and toluene estimated to be ca. 16 in DMSO) the reaction shows all the characteristics of a deprotonation mechanism, the reaction rate being strongly dependent on the toluene para substituent (=4.8(±0.3)), and displaying substantial and rate-limiting primary (kH/kD=4.2(±0.6)) and secondary (kH/kD=1.18(±0.08)) kinetic isotope effects on the deuteration of the toluene methyl group. The reaction is catalysed by K-HMDS, but proceeds without cross over between toluene methyl protons and does not involve an HMDS anion acting as base to generate a benzyl anion. Detailed analysis of the reaction kinetics/kinetic isotope effects demonstrates that a pseudo-first-order decay in 2 arises from a first-order dependence on 2, a first-order dependence on toluene (in large excess) and, in the catalytic manifold, a complex noninteger dependence on the K-HMDS dimer. The rate is not satisfactorily predicted by equations based on the Brønsted salt-effect catalysis law. However, the rate can be satisfactorily predicted by a mole-fraction-weighted net rate constant: -d[2]/dt=({x2 kuncat}+{(1-x2) kcat})[2]1[toluene]1, in which x2 is determined by a standard bimolecular complexation equilibrium term. The association constant (Ka) for rapid equilibrium-complexation of 2 with (K-HMDS)2 to form [2(K-HMDS)2] is extracted by nonlinear regression of the 13C NMR shift of C(2) in [13C1]-2 versus [(K-HMDS)2] yielding: Ka=62(±7) M-1; C(2) in 2=237.0 ppm; C(2) in [2(K-HMDS)2]=226.8 ppm. It is thus concluded that there is discrete, albeit inefficient, molecular catalysis through the 1:1 carbene/(K-HMDS)2 complex [2(K-HMDS)2], which is found to react with toluene more rapidly than free 2 by a factor of 3.4 (=kcat/kuncat). The greater reactivity of the complex [2(K-HMDS)2] over the free carbene (2) may arise from local Brønsted salt-effect catalysis by the (K-HMDS)2 liberated in the solvent cage upon reaction with toluene.
Translated title of the contributionIntermolecular Insertion of an N,N-Heterocyclic Carbene into a Nonacidic C-H Bond: Kinetics, Mechanism and Catalysis by (K-HMDS)2 (HMDS=Hexamethyldisilazide)
Original languageEnglish
Pages (from-to)5361 - 5375
Number of pages15
JournalChemistry - A European Journal
Volume12 (20)
DOIs
Publication statusPublished - Jul 2006

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Publisher: Wiley

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